CN111533689B - 2,2' -biquinoline compound and one-pot preparation method thereof - Google Patents
2,2' -biquinoline compound and one-pot preparation method thereof Download PDFInfo
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- CN111533689B CN111533689B CN202010465462.6A CN202010465462A CN111533689B CN 111533689 B CN111533689 B CN 111533689B CN 202010465462 A CN202010465462 A CN 202010465462A CN 111533689 B CN111533689 B CN 111533689B
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/20—Oxygen atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/04—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to the ring carbon atoms
- C07D215/06—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to the ring carbon atoms having only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, attached to the ring nitrogen atom
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/18—Halogen atoms or nitro radicals
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- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
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Abstract
The invention relates to a 2,2' -biquinoline compound and a one-pot preparation method thereof. The method comprises the following steps: the preparation method adopts cheap and easily available raw materials, is simple, has mild reaction conditions, adopts a one-pot method with a short synthetic route to carry out the contact reaction, has the yield of up to 81.0 percent, and provides a feasible method for industrially preparing the compound.
Description
Technical Field
The invention relates to a 2,2' -biquinoline compound and a one-pot preparation method thereof, belonging to the technical field of organic and pharmaceutical synthesis.
Background
The 2,2' -biquinoline compound is a nitrogenous heterocyclic compound with important functions and is widely applied to a plurality of fields of medicines, biological analysis, luminescent materials and the like. The 2,2 '-biquinoline compound can form a metal complex of a conjugated system with various metal ions, plays an important role in trace metal detection and content measurement, and for example, the iron content in industrial caprolactam is measured by utilizing the mechanism that 2,2' -biquinoline and ferrous ions generate a red complex. The synthesis of 2,2' -biquinoline compounds has been the focus of research in recent years due to their excellent physicochemical properties.
At present, the synthesis methods of 2,2' -biquinoline compounds reported in domestic and foreign documents mainly comprise the following steps:
(1) The early synthesis method is to utilize transition metal to catalyze nucleophilic substitution reaction between halogenated quinoline and Grignard reagent of quinoline to obtain 2,2' -biquinoline compounds. The method has obvious defects: firstly, the transition metal is expensive, and the byproduct metal salt of the reaction is easy to be harmful to the environment; on the other hand, the method needs to prepare the quinoline into halogenated quinoline and Grignard reagent of the quinoline, so that the experimental operation becomes complicated, the production cost is increased, and the industrial production is not facilitated.
(2) In 2001, kazuhiro et al reported a simple synthesis method of 2,2' -biquinoline compounds: heating for 2h in a diglyme solvent system at a reflux temperature (160 ℃) to generate the 2,2' -biquinoline compound through coupling of the o-cyano styrenes. The reaction temperature is high, and the solvent diglyme is flammable liquid and has certain harm to human bodies; the method also needs to prepare the o-cyano styrene from the o-amino styrene, the production cost is high, and the prepared o-cyano styrene has unstable physicochemical properties and needs to be stored at a low temperature.
(3) In 2011, yuta Araki et al proposed the method of: the phosphazene ligand P4-tertiary butyl is used as an organic catalyst, trimethyl silane diethyl amine is used for deprotonating quinoline-N-oxide, and the addition-elimination reaction is carried out on the quinoline-N-oxide and another quinoline-N-oxide to obtain dimer 2,2' -biquinoline-N-oxide. The method needs to react for 24 hours at room temperature, has long reaction time and low yield (only 40 percent); the organic catalyst phosphazene ligand P4-tertiary butyl is high in price and production cost.
In summary, the above methods for synthesizing 2,2' -biquinoline compounds have the disadvantages of difficult generation, harsh reaction conditions, low yield, few applicable substrates or high toxicity or difficult acquisition of raw materials, expensive catalysts and the like.
Disclosure of Invention
In order to solve the defects in the prior art, the invention aims to provide a 2,2' -biquinoline compound and a one-pot preparation method thereof. The method has the advantages of mild reaction conditions, wide substrate range, low price and easy acquisition of raw materials, good safety and high yield.
The invention provides a 2,2' -biquinoline compound, which has a structure shown in a general formula I:
wherein R is 1 Is hydrogen, fluorine, chlorine, bromine, phenyl, methyl, methoxy or ethoxy;
R 2 methyl, ethyl, methoxy, phenyl, chloro or bromo;
R 3 is a straight chain or branched alkane having 1 to 4 carbon atoms, benzyl or phenyl.
Further, the compound of formula I is selected from one of the following compounds I-1 to I-15:
the invention also provides a one-pot preparation method of the 2,2' -biquinoline compound, which comprises the following steps:
(1) Under the catalysis of a catalyst iodine simple substance, the compound 1 is contacted with the iodine simple substance in advance to obtain a contacted product;
(2) Then the product after contact is contacted with a compound 2 and a compound 3 under the catalysis of potassium carbonate; finally, extracting, washing, drying, separating and purifying to obtain the 2,2' -biquinoline compound
Wherein R is 1 Is hydrogen, fluorine, chlorine, bromine, phenyl, methyl, methoxy or ethoxy;
R 2 methyl, ethyl, methoxy, phenyl, chloro or bromo;
R 3 is a straight chain or branched alkane having 1 to 4 carbon atoms, benzyl or phenyl.
Further, the molar ratio of the compound 1 to the compound 2 to the compound 3 is 1 (0.8-2) to 0.8-2.
Further, the molar ratio of the compound 1 to the iodine simple substance is 1 (1.5-3).
Further, the molar ratio of the compound 1 to the potassium carbonate is 1 (0.1-2).
Further, the compound 1 is contacted with iodine simple substance in advance, specifically: adding the compound 1, the catalyst 1 and the solvent into a pressure-resistant pipe, heating in an oil bath at 60-150 ℃ for reaction for 2-8 hours, monitoring the reaction by TLC, and obtaining a product after contact after the compound 1 is completely converted.
Further, the solvent is dimethyl sulfoxide, ethyl acetate, acetonitrile, methanol, ethanol, toluene or chloroform.
Further, the product after contact is contacted with the compound 2 and the compound 3 under the catalysis of potassium carbonate, specifically: adding a compound 2, a compound 3 and potassium carbonate into the product after contact, heating in an oil bath at 60-150 ℃ for reaction for 2-8 hours, cooling to room temperature after the reaction is finished, adding 30-50mL of water into the reaction liquid, extracting the mixed liquid, washing an organic layer, collecting an organic phase, adding anhydrous sodium sulfate for drying, decompressing and evaporating a solvent to obtain a crude product, and separating and purifying the crude product to obtain the 2,2' -biquinoline compound.
Further, the extracting agent for extraction is ethyl acetate; the washing detergent is sodium thiosulfate and sodium hydroxide; the separation and purification steps are as follows: and (3) performing column chromatography separation and purification by using a mixture of ethyl acetate and petroleum ether as leacheate, wherein the volume ratio of the ethyl acetate to the petroleum ether is 1 (1-10).
The beneficial effects are that: compared with the existing method, the synthesis method provided by the invention has the advantages of greatly shortened reaction time, mild reaction condition, good safety, simplicity and convenience in operation, wide substrate range, low price and easiness in obtaining.
Detailed Description
The preparation method has the outstanding substantial characteristics that a series reaction strategy is utilized, multi-step reaction is integrated in one pot, combined molecular iodine is not only used as a key effect of a catalyst and an oxidant in the reaction, an intermediate 2- (iodomethyl) -quinoline compound 6a and a 2-aldehyde quinoline compound 5a, 2-aldehyde quinoline compound 5a and an aromatic amine generate an imine intermediate, simultaneously, the aromatic amine and substituted acetaldehyde generate an enamine intermediate, then [4+2] cycloaddition is carried out on the enamine intermediate and the imine intermediate to generate a final target product 2,2' -biquinoline compound, and the reaction process is shown as a formula (I):
the control experiment result shows that the 2-methylquinoline compound can be oxidized to generate an intermediate 2-aldehyde quinoline compound 5a at 110 ℃ in dimethyl sulfoxide under the action of molecular iodine, and the reaction result is shown as a formula (II):
the 2-aldehyde quinoline compound 5a reacts with aromatic amine and substituted acetaldehyde in DMSO at 110 ℃ for 4-6 hours under the action of iodine and potassium carbonate, and the target product 2,2' -biquinoline can be obtained with 75% yield, and is shown in a formula (III).
The above related mechanism researches prove that 2- (iodomethyl) -quinoline compounds 6a and 2-aldehyde quinoline compounds 5a are intermediates of reaction experience, the invention does not need to separate related intermediates, molecular iodine can promote raw material 2-methylquinoline compounds to directly generate intermediates 2- (iodomethyl) -quinoline compounds 6a and 2-aldehyde quinoline compounds 5a in situ, then the 2-aldehyde quinoline compounds 5a and aromatic amine generate imine intermediates, meanwhile, aromatic amine and substituted acetaldehyde can generate enamine intermediates in situ, and finally, the imine intermediates and the enamine intermediates generate [4+2] cyclization reaction to generate target products 2,2' -biquinoline.
The invention is catalyzed by the catalyst, the methylquinoline compound is contacted with the catalyst in advance to obtain a contacted product, and the contacted product is contacted with the substituted aniline compound, phenylacetaldehyde or substituted acetaldehyde under the catalysis of potassium carbonate. For a better understanding of the present invention, the following examples are set forth to further illustrate the invention.
Example 1:
is synthesized by (a)
The reaction formula is:
the method comprises the following specific steps: to a 15mL pressure-resistant tube was added 0.5mmol of 2, 6-dimethylquinoline, 0.75mmol of elemental iodine and 2.0mL of dimethyl sulfoxide. Sealing a pressure-resistant pipe, heating the reaction for 4-6h in an oil bath at 110 ℃, monitoring the reaction by TLC, after methylquinoline is completely converted, adding 0.5mmol of 4-methylaniline, 0.5mmol of phenylacetaldehyde and 0.25mmol of potassium carbonate into the reaction liquid, continuing to react for 4-6h under the same conditions, cooling to room temperature after the reaction is finished, adding 50ml of water into the reaction liquid, extracting the mixed liquid by using ethyl acetate, washing an organic layer by using sodium thiosulfate and sodium hydroxide, collecting an organic phase, adding anhydrous sodium sulfate for drying, removing a solvent by decompression, and performing column separation and purification on the crude product by using ethyl acetate/petroleum ether=1:5 (V/V) as eluent to obtain the required product. The product is white solid, the yield is 81.0%, the melting point is 127.5-128.0 ℃, the melting range of the product is shorter, and the product is purer.
The nuclear magnetic hydrogen spectrogram result of the obtained product is as follows: 1 H NMR(400MHz,CDCI 3 ):δ(ppm)8.19(d,J＝10.8Hz,2H),7.94(t,J＝9.3Hz,2H),7.65(s,1H),7.58(dd,J＝8.7,2.3Hz,1H),7.50(dd,J＝11.1,2.7Hz,2H),7.44(d,J＝8.5Hz,1H),7.27–7.23(m,2H),7.21(dd,J＝4.4,2.8Hz,3H),2.57(s,3H),2.51(s,3H).
13 C NMR(100MHz,CDCI 3 ):δ(ppm)157.41,156.15,146.32,145.80,139.81,137.26,137.15,136.70,135.11,134.76,132.08,131.72,129.56,128.12,127.77,127.17,126.96,126.27,126.21,122.53,21.72,21.61.
example 2:
is synthesized by (a)
The reaction formula is:
the method comprises the following specific steps: to a 15mL pressure-resistant tube was added 0.5mmol of 6-methoxy-2-methylquinoline, 0.75mmol of elemental iodine and 2.0mL of dimethyl sulfoxide. Sealing a pressure-resistant pipe, heating the reaction for 4-6h in an oil bath at 110 ℃, monitoring the reaction by TLC, after methylquinoline is completely converted, adding 0.5mmol of 4-methylaniline, 0.5mmol of phenylacetaldehyde and 0.25mmol of potassium carbonate into the reaction liquid, continuing the reaction for 4-6h under the same conditions, cooling to room temperature after the reaction is finished, adding 50ml of water into the reaction liquid, extracting the mixed liquid by using ethyl acetate, washing an organic layer by using sodium thiosulfate and sodium hydroxide, collecting an organic phase, adding anhydrous sodium sulfate for drying, evaporating the solvent under reduced pressure to obtain a crude product, and performing column separation and purification on the crude product by using ethyl acetate/petroleum ether=1:5 (V/V) as eluent to obtain the required product. The product is white solid, the yield is 80.5%, the melting point is 120.0-120.8 ℃, the melting range of the product is shorter and the product is purer.
The nuclear magnetic hydrogen spectrogram result of the obtained product is as follows: 1 H NMR(400MHz,CDCI 3 ):δ(ppm)8.17(d,J＝1.2Hz,2H),7.93(dd,J＝9.2,6.0Hz,2H),7.64(s,1H),7.59(dd,J＝8.8,2.4Hz,1H),7.45(d,J＝8.5Hz,1H),7.33(dd,J＝9.2,2.8Hz,1H),7.26-7.24(m,2H),7.23(q,J＝4.0Hz,3H),7.01(d,J＝2.8Hz,1H),3.90(s,3H),2.56(s,3H).
13 C NMR(100MHz,CDCI 3 ):δ(ppm)158.44,158.42,154.58,147.85,143.42,139.79,136.57,135.65,135.05,131.36,129.96,129.57,129.32,128.86,128.14,127.34,127.08,127.03,126.68,122.65,122.57,104.71,55.56.
example 3:
is synthesized by the following steps:
the reaction formula is:
the method comprises the following specific steps: to a 15mL pressure-resistant tube was added 0.5mmol of 6-fluoro-2-methylquinoline, 0.75mmol of elemental iodine and 2.0mL of dimethyl sulfoxide. Sealing a pressure-resistant pipe, heating the reaction for 4-6h in an oil bath at 110 ℃, monitoring the reaction by TLC, after methylquinoline is completely converted, adding 0.5mmol of 4-methylaniline, 0.5mmol of phenylacetaldehyde and 0.25mmol of potassium carbonate into the reaction liquid, continuing to react for 4-6h under the same conditions, cooling to room temperature after the reaction is finished, adding 50ml of water into the reaction liquid, extracting the mixed liquid by using ethyl acetate, washing an organic layer by using sodium thiosulfate and sodium hydroxide, collecting an organic phase, adding anhydrous sodium sulfate for drying, removing a solvent by decompression, and performing column separation and purification on the crude product by using ethyl acetate/petroleum ether=1:3 (V/V) as eluent to obtain the required product. The product is white solid, the yield is 74.5%, the melting point is 170.7-171.7 ℃, the melting range of the product is shorter, and the product is purer.
The nuclear magnetic hydrogen spectrogram result of the obtained product is as follows: 1 H NMR(400MHz,CDCI 3 ):δ(ppm)8.17(d,J＝8.4Hz,2H),8.03-7.95(m,2H),7.66(s,1H),7.59(dd,J＝8.8,2.0Hz,1H),7.55(d,J＝8.5,0.8Hz,1H),7.46-7.33(m,2H),7.25-7.21(m,5H),2.58(s,3H).
13 C NMR(100MHz,CDCI 3 ):δ(ppm)161.87,159.40,157.84,157.81,155.79,145.86,139.78,137.43,137.21,135.11,135.05,134.73,132.48,132.39,132.18,129.56,128.17,127.70,127.05,123.27,119.76,119.51,110.48,110.26,21.74.
example 4:
is synthesized by (a)
The reaction formula is:
the method comprises the following specific steps: to a 15mL pressure-resistant tube was added 0.5mmol of 7-chloro-2-methylquinoline, 0.75mmol of elemental iodine and 2.0mL of dimethyl sulfoxide. Sealing a pressure-resistant pipe, heating the reaction for 4-6h in an oil bath at 110 ℃, monitoring the reaction by TLC, after methylquinoline is completely converted, adding 0.5mmol of 4-methylaniline, 0.5mmol of phenylacetaldehyde and 0.25mmol of potassium carbonate into the reaction liquid, continuing to react for 4-6h under the same conditions, cooling to room temperature after the reaction is finished, adding 50ml of water into the reaction liquid, extracting the mixed liquid by using ethyl acetate, washing an organic layer by using sodium thiosulfate and sodium hydroxide, collecting an organic phase, adding anhydrous sodium sulfate for drying, removing a solvent by decompression, and performing column separation and purification on the crude product by using ethyl acetate/petroleum ether=1:3 (V/V) as eluent to obtain the required product. The product is white solid, the yield is 75.5%, the melting point is 151.7-152.2 ℃, the melting range of the product is shorter, and the product is purer.
The nuclear magnetic hydrogen spectrogram result of the obtained product is as follows: 1 H NMR(400MHz,CDCI 3 ):δ(ppm)8.18(s,2H),8.05–7.95(m,2H),7.69(d,J＝8.7Hz,1H),7.59(dd,J＝8.4,2.2Hz,1H),7.56(d,J＝8.4Hz,1H),7.45(dd,J＝8.7,2.2Hz,1H),7.28–7.18(m,6H),2.57(s,3H).
13 C NMR(100MHz,CDCI 3 ):δ(ppm)159.49,155.67,148.07,145.79,139.65,137.49,137.19,135.57,135.19,134.72,132.19,129.49,128.80,128.57,128.17,127.82,127.77,127.09,126.30,125.45,122.74,21.72.
example 5:
is synthesized by (a)
The reaction formula is:
the method comprises the following specific steps: to a 15mL pressure-resistant tube was added 0.5mmol of 6-bromo-2-methylquinoline, 0.75mmol of elemental iodine and 2.0mL of dimethyl sulfoxide. Sealing a pressure-resistant pipe, heating the reaction for 4-6h in an oil bath at 110 ℃, monitoring the reaction by TLC, after methylquinoline is completely converted, adding 0.5mmol of 4-methylaniline, 0.5mmol of phenylacetaldehyde and 0.25mmol of potassium carbonate into the reaction liquid, continuing to react for 4-6h under the same conditions, cooling to room temperature after the reaction is finished, adding 50ml of water into the reaction liquid, extracting the mixed liquid by using ethyl acetate, washing an organic layer by using sodium thiosulfate and sodium hydroxide, collecting an organic phase, adding anhydrous sodium sulfate for drying, removing a solvent by decompression, and performing column separation and purification on the crude product by using ethyl acetate/petroleum ether=1:3 (V/V) as eluent to obtain the required product. The product is white solid, the yield is 77.5%, the melting point is 156.0-156.5 ℃, the melting range of the product is shorter and the product is purer.
The nuclear magnetic hydrogen spectrogram result of the obtained product is as follows: 1 H NMR(400MHz,CDCI 3 ):δ(ppm)8.18(d,J＝12.0Hz,2H),7.95(q,J＝8.28,10.72Hz,2H),7.85(d,J＝9.0Hz,1H),7.71(dd,J＝9.0,4.0Hz,1H),7.66(s,1H),7.61(dd,J＝10.08,1.84Hz,2H),7.23(s,5H),2.58(s,3H).
13 C NMR(100MHz,CDCI 3 ):δ(ppm)158.83,155.67,146.33,145.85,139.71,137.52,137.23,134.73,132.88,132.22,131.64,129.54,129.50,129.43,128.20,128.19,127.84,127.07,126.32,123.39,120.68,21.75.
example 6:
is synthesized by (a)
The reaction formula is:
the method comprises the following specific steps: to a 15mL pressure-resistant tube were added 0.5mmol of 4-methylquinoline, 0.75mmol of elemental iodine and 2.0mL of dimethyl sulfoxide. Sealing a pressure-resistant pipe, heating the reaction for 4-6h in an oil bath at 110 ℃, monitoring the reaction by TLC, after methylquinoline is completely converted, adding 0.5mmol of 4-methylaniline, 0.5mmol of phenylacetaldehyde and 0.25mmol of potassium carbonate into the reaction liquid, continuing the reaction for 4-6h under the same conditions, cooling to room temperature after the reaction is finished, adding 50ml of water into the reaction liquid, extracting the mixed liquid by using ethyl acetate, washing an organic layer by using sodium thiosulfate and sodium hydroxide, collecting an organic phase, adding anhydrous sodium sulfate for drying, evaporating the solvent under reduced pressure to obtain a crude product, and performing column separation and purification on the crude product by using ethyl acetate/petroleum ether=1:8 (V/V) as eluent to obtain the required product. The product is white solid, the yield is 76.9%, the melting point is 170.9-171.3 ℃, the melting range of the product is shorter and purer.
The nuclear magnetic hydrogen spectrogram result of the obtained product is as follows: 1 H NMR(400MHz,CDCI 3 ):δ(ppm)8.80(d,J＝4.4Hz,1H),8.23(s,1H),8.10(dd,J＝12.4,8.5Hz,2H),7.77–7.71(m,2H),7.69–7.59(m,2H),7.45–7.38(m,1H),7.23(d,J＝4.5Hz,1H),7.11(s,5H),2.60(s,3H).
13 C NMR(100MHz,CDCI 3 ):δ(ppm)δ154.64,149.25,148.30,146.92,145.59,138.66,137.64,136.74,135.49,132.49,129.49,129.42,129.12,128.19,127.67,127.46,126.94,126.84,126.41,125.97,122.36,21.73.
example 7:
is synthesized by (a)
The reaction formula is:
the method comprises the following specific steps: to a 15mL pressure-resistant tube was added 0.5mmol of 2-chloro-4-methylquinoline, 0.75mmol of elemental iodine and 2.0mL of dimethyl sulfoxide. Sealing a pressure-resistant pipe, heating the reaction for 4-6h in an oil bath at 110 ℃, monitoring the reaction by TLC, after methylquinoline is completely converted, adding 0.5mmol of 4-methylaniline, 0.5mmol of phenylacetaldehyde and 0.25mmol of potassium carbonate into the reaction liquid, continuing to react for 4-6h under the same conditions, cooling to room temperature after the reaction is finished, adding 50ml of water into the reaction liquid, extracting the mixed liquid by using ethyl acetate, washing an organic layer by using sodium thiosulfate and sodium hydroxide, collecting an organic phase, adding anhydrous sodium sulfate for drying, removing a solvent by decompression, and performing column separation and purification on the crude product by using ethyl acetate/petroleum ether=1:2 (V/V) as eluent to obtain the required product. The product is white solid, the yield is 76.5%, the melting point is 152.2-152.6 ℃, the melting range of the product is shorter, and the product is purer.
The nuclear magnetic hydrogen spectrogram result of the obtained product is as follows: 1 H NMR(400MHz,CDCI 3 ):δ(ppm)8.20(s,1H),8.09(d,J＝8.0Hz,1H),7.71(s,1H),7.64(dd,J＝8.68,1.64Hz,1H),7.44-7.40(m,2H),7.31(d,J＝7.8Hz,1H),7.24(t,J＝2.4Hz,2H),7.20(t,J＝4.0Hz,3H),7.05(t,J＝4.0Hz,1H),6.60(s,1H),2.60(s,3H).
13 C NMR(100MHz,CDCI 3 ):δ(ppm)153.75,151.70,145.51,138.71,138.43,137.90,137.05,135.22,132.68,130.75,129.19,129.10,128.53,127.87,126.82,126.52,122.75,122.54,119.80,116.49,21.84.
example 8:
is synthesized by (a)
The reaction formula is:
the method comprises the following specific steps: to a 15mL pressure-resistant tube was added 0.5mmol of 2-methylquinoline, 0.75mmol of elemental iodine and 2.0mL of dimethyl sulfoxide. Sealing a pressure-resistant pipe, heating in an oil bath at 110 ℃ for reaction for 4-6h, monitoring the reaction by TLC, after methylquinoline is completely converted, adding 0.5mmol of 3, 5-dimethylaniline, 0.5mmol of phenylacetaldehyde and 0.25mmol of potassium carbonate into the reaction liquid, continuously reacting for 4-6h under the same condition, cooling to room temperature after the reaction is finished, adding 50ml of water into the reaction liquid, extracting the mixed liquid by using ethyl acetate, washing an organic layer by using sodium thiosulfate and sodium hydroxide, collecting an organic phase, adding anhydrous sodium sulfate for drying, removing a solvent by decompression, and performing column separation and purification on the crude product by using ethyl acetate/petroleum ether=1:5 (V/V) as eluent to obtain the required product. The product is white solid, the yield is 78.6%, the melting point is 145.6-146.0 ℃, the melting range of the product is shorter and the product is purer.
The nuclear magnetic hydrogen spectrogram result of the obtained product is as follows: 1 H NMR(400MHz,CDCI 3 ):δ(ppm)8.37(s,1H),8.06(dd,J＝17.48,8.48Hz,3H),7.78(dd,J＝8.0,1.2Hz,1H),7.66(td,J＝8.8,1.6Hz,1H),7.56(d,J＝8.4Hz,1H),7.52(td,J＝8.0,1.2Hz,1H),7.29-7.26(m,3H),7.24-7.21(m,3H),2.71(s,3H),2.55(s,3H).
13 C NMR(100MHz,CDCI 3 ):δ(ppm)135.88,134.02,133.59,130.35,129.88,129.46,128.20,127.38,127.20,126.99,126.84,125.29,122.54,21.94,18.60.
example 9:
is synthesized by (a)
The reaction formula is:
the method comprises the following specific steps: to a 15mL pressure-resistant tube was added 0.5mmol of 2-methylquinoline, 0.75mmol of elemental iodine and 2.0mL of dimethyl sulfoxide. Sealing a pressure-resistant pipe, heating the reaction for 4-6h in an oil bath at 110 ℃, monitoring the reaction by TLC, after methylquinoline is completely converted, adding 0.5mmol of 4-ethylaniline, 0.5mmol of phenylacetaldehyde and 0.25mmol of potassium carbonate into the reaction liquid, continuing the reaction for 4-6h under the same conditions, cooling to room temperature after the reaction is finished, adding 50ml of water into the reaction liquid, extracting the mixed liquid by using ethyl acetate, washing an organic layer by using sodium thiosulfate and sodium hydroxide, collecting an organic phase, adding anhydrous sodium sulfate for drying, evaporating the solvent under reduced pressure to obtain a crude product, and performing column separation and purification on the crude product by using ethyl acetate/petroleum ether=1:6 (V/V) as eluent to obtain the required product. The product is white solid, the yield is 75.8%, the melting point is 138.8-140.1 ℃, the melting range of the product is shorter and the product is purer.
The nuclear magnetic hydrogen spectrogram result of the obtained product is as follows: 1 H NMR(400MHz,CDCI 3 ):δ(ppm)8.23(d,J＝7.6Hz,2H),8.04(t,J＝6.4Hz,2H),7.76(dd,J＝8.0,1.2Hz,1H),7.67(q,J＝8.0,Hz,2H),7.65-7.60(m,1H),7.54-7.48(m,2H),7.28-7.24(m,2H),7.21(t,J＝3.2Hz,3H),2.88(q,J＝7.6Hz,2H),1.37(t,J＝7.6Hz,3H).
13 C NMR(100MHz,CDCI 3 ):δ(ppm)158.33,156.03,147.74,145.98,143.54,139.76,137.40,135.78,134.73,131.11,129.91,129.60,129.58,129.39,128.14,127.85,127.35,127.13,127.00,126.76,124.93,122.54,28.94,15.23.
example 10:
is synthesized by (a)
The reaction formula is:
the method comprises the following specific steps: to a 15mL pressure-resistant tube was added 0.5mmol of 2-methylquinoline, 0.75mmol of elemental iodine and 2.0mL of dimethyl sulfoxide. Sealing a pressure-resistant pipe, heating the reaction for 4-6h in an oil bath at 110 ℃, monitoring the reaction by TLC, after methylquinoline is completely converted, adding 0.5mmol of biphenyl-2-amine, 0.5mmol of phenylacetaldehyde and 0.25mmol of potassium carbonate into the reaction liquid, continuing to react for 4-6h under the same condition, cooling to room temperature after the reaction is finished, adding 50ml of water into the reaction liquid, extracting the mixed liquid by using ethyl acetate, washing an organic layer by using sodium thiosulfate and sodium hydroxide, collecting an organic phase, adding anhydrous sodium sulfate for drying, removing a solvent by decompression, and performing column separation and purification on the crude product by using ethyl acetate/petroleum ether=1:5 (V/V) as eluent to obtain a required product. The product is white solid, the yield is 77.8%, the melting point is 145.5-150.0 ℃, the melting range of the product is shorter and the product is purer.
The nuclear magnetic hydrogen spectrogram result of the obtained product is as follows: 1 H NMR(400MHz,CDCI 3 ):δ(ppm)8.31(s,1H),8.14(dd,J＝28.0,8.0Hz,2H),7.90(ddd,J＝9.4,8.0,1.4Hz,3H),7.85(dd,J＝8.0,4.0Hz,1H),7.74(d,J＝12.0Hz,1H),7.66(t,J＝7.4Hz,1H),7.52(td,J＝7.0,1.6Hz,1H),7.54-7.49(m,2H),7.49-7.38(m,3H),7.35-7.30(m,2H),7.29-7.26(m,3H).
13 C NMR(100MHz,CDCI 3 ):δ(ppm)158.05,144.51,140.89,140.76,139.41,138.52,136.16,135.24,131.22,130.47,129.69,129.47,129.27,128.30,128.04,127.86,127.40,127.37,127.34,126.78,126.73,122.36.
example 11:
is synthesized by (a)
The reaction formula is:
the method comprises the following specific steps: to a 15mL pressure-resistant tube was added 0.5mmol of 2-methylquinoline, 0.75mmol of elemental iodine and 2.0mL of dimethyl sulfoxide. Sealing a pressure-resistant pipe, heating the reaction for 4-6h in an oil bath at 110 ℃, monitoring the reaction by TLC, after methylquinoline is completely converted, adding 0.5mmol of p-methoxyaniline, 0.5mmol of phenylacetaldehyde and 0.25mmol of potassium carbonate into the reaction liquid, continuing the reaction for 4-6h under the same condition, cooling to room temperature after the reaction is finished, adding 50ml of water into the reaction liquid, extracting the mixed liquid by using ethyl acetate, washing an organic layer by using sodium thiosulfate and sodium hydroxide, collecting an organic phase, adding anhydrous sodium sulfate for drying, evaporating the solvent under reduced pressure to obtain a crude product, and separating and purifying the crude product by using ethyl acetate/petroleum ether=1:5 (V/V) as eluent to obtain the required product. The product is white solid, the yield is 76.2%, the melting point is 186.1-186.8 ℃, the melting range of the product is shorter and the product is purer.
The nuclear magnetic hydrogen spectrogram result of the obtained product is as follows: 1 H NMR(400MHz,CDCI 3 ):δ(ppm)8.17(td,J＝9.2,0.36Hz,2H),8.06-8.0(m,2H),7.77(dd,J＝8.0,4.0Hz,1H),7.70-7.61(m,1H),7.55-7.49(m,1H),7.49(t,J＝1.24Hz,1H),7.42(dd,J＝9.2,2.88Hz,1H),7.29-7.24(m,2H),7.24-7.20(m,3H),7.15(d,J＝3.0Hz,1H),3.96(s,3H).
13 C NMR(100MHz,CDCI 3 ):δ(ppm)158.43,154.58,147.85,143.42,139.79,136.57,135.65,135.05,131.36,129.96,129.57,129.32,128.86,128.14,127.34,127.34,127.08,127.03,126.68,122.61,104.71,77.32,77.00,76.68,55.56.
example 12:
the reaction formula is:
the method comprises the following specific steps: to a 15mL pressure-resistant tube was added 0.5mmol of 2-methylquinoline, 0.75mmol of elemental iodine and 2.0mL of dimethyl sulfoxide. Sealing a pressure-resistant pipe, heating for reaction for 4-6h in an oil bath at 110 ℃, monitoring the reaction by TLC, adding 0.5mmol of p-methylaniline, 0.5mmol of propionaldehyde and 0.25mmol of potassium carbonate into the reaction liquid after the methylquinoline is completely converted, continuing to react for 4-6h under the same condition, cooling to room temperature after the reaction is finished, adding 50ml of water into the reaction liquid, extracting the mixed liquid by using ethyl acetate, washing an organic layer by using sodium thiosulfate and sodium hydroxide, collecting an organic phase, adding anhydrous sodium sulfate for drying, evaporating the solvent under reduced pressure to obtain a crude product, and separating and purifying the crude product by using ethyl acetate/petroleum ether=1:8 (V/V) as eluent to obtain the required product. The product is white solid, the yield is 77.3%, the melting point is 97.5-97.8 ℃, the melting range of the product is shorter and the product is purer.
The nuclear magnetic hydrogen spectrogram result of the obtained product is as follows: 1 H NMR(400MHz,CDCI 3 ):δ(ppm)8.30(dd,J＝8.7,1.0Hz,1H),8.17(ddd,J＝8.5,2.0,0.8Hz,1H),8.08(d,J＝8.5Hz,1H),7.97(s,1H),7.87(dd,J＝8.3,1.8Hz,1H),7.77–7.69(m,1H),7.61–7.56(m,1H),7.55(dd,J＝2.5,1.1Hz,1H),7.50(dd,J＝8.7,2.2Hz,1H),2.72(d,J＝1.1Hz,3H),2.54(s,3H).
13 C NMR(100MHz,CDCI 3 ):δ(ppm)159.02,156.95,147.39,145.17,137.09,136.91,136.70,131.21,130.54,129.81,129.62,129.16,128.24,127.68,127.52,126.89,125.71,21.81,20.83.
example 13:
the reaction formula is:
the method comprises the following specific steps: to a 15mL pressure-resistant tube was added 0.5mmol of 2-methylquinoline, 0.75mmol of elemental iodine and 2.0mL of dimethyl sulfoxide. Sealing a pressure-resistant pipe, heating for reaction for 4-6h in an oil bath at 110 ℃, monitoring the reaction by TLC, adding 0.5mmol of p-methylaniline, 0.5mmol of butyraldehyde and 0.25mmol of potassium carbonate into the reaction liquid after the methylquinoline is completely converted, continuing to react for 4-6h under the same condition, cooling to room temperature after the reaction is finished, adding 50ml of water into the reaction liquid, extracting the mixed liquid by using ethyl acetate, washing an organic layer by using sodium thiosulfate and sodium hydroxide, collecting an organic phase, adding anhydrous sodium sulfate for drying, evaporating the solvent under reduced pressure to obtain a crude product, and separating and purifying the crude product by using ethyl acetate/petroleum ether=1:8 (V/V) as eluent to obtain the required product. The product is white solid, the yield is 75.3%, the melting point is 95.1-95.7 ℃, the melting range of the product is shorter, and the product is purer.
The nuclear magnetic hydrogen spectrogram result of the obtained product is as follows: 1 H NMR(400MHz,CDCI 3 ):δ(ppm)8.32(dd,J＝8.0,0.8Hz,1H),8.16(dt,J＝8.5,1.0Hz,1H),8.05(d,J＝8.7Hz,1H),8.02(t,J＝3.2Hz,2H),7.90(dd,J＝12.0,4.0Hz,1H),7.78-7.69(m,1H),7.62-7.54(m,2H),7.52(dd,J＝8.4,2.4Hz,1H),3.13(ddd,J＝8.6,7.6,0.6Hz,2H),2.55(d,J＝1.3Hz,3H),1.22(t,J＝7.1Hz,3H).
13 C NMR(100MHz,CDCI 3 ):δ(ppm)147.41,144.86,136.76,136.46,135.53,131.33,129.83,129.65,129.02,128.35,127.69,127.54,126.89,125.93,122.25,77.43,77.12,76.80,26.18,21.80,15.09.
example 14:
is synthesized by (a)
The reaction formula is:
the method comprises the following specific steps: to a 15mL pressure-resistant tube was added 0.5mmol of 2-methylquinoline, 0.75mmol of elemental iodine and 2.0mL of dimethyl sulfoxide. Sealing a pressure-resistant pipe, heating the reaction for 4-6h in an oil bath at 110 ℃, monitoring the reaction by TLC, after methylquinoline is completely converted, adding 0.5mmol of p-methylaniline, 0.5mmol of isovaleraldehyde and 0.25mmol of potassium carbonate into the reaction liquid, continuing the reaction for 4-6h under the same conditions, cooling to room temperature after the reaction is finished, adding 50ml of water into the reaction liquid, extracting the mixed liquid by using ethyl acetate, washing an organic layer by using sodium thiosulfate and sodium hydroxide, collecting an organic phase, adding anhydrous sodium sulfate for drying, evaporating the solvent under reduced pressure to obtain a crude product, and performing column separation and purification on the crude product by using ethyl acetate/petroleum ether=1:10 (V/V) as eluent to obtain the required product. The product is white solid, the yield is 76.4%, the melting point is 90.1-90.6 ℃, the melting range of the product is shorter, and the product is purer.
The nuclear magnetic hydrogen spectrogram result of the obtained product is as follows: 1 H NMR(400MHz,CDCI 3 ):δ(ppm)8.32(dd,J＝8.5,0.6Hz,1H),8.16(dq,J＝2.6,0.8Hz,1H),8.12(s,1H),8.04(d,J＝8.6Hz,1H),7.91(d,J＝8.4Hz,1H),7.90(dd,J＝8.2,1.4Hz,1H),7.77-7.71(m,1H),7.61(s,1H),7.60-7.55(m,1H),7.52(dd,J＝8.5,2.0Hz,1H),3.76-3.66(m,1H),2.55(s,3H),1.28(d,J＝6.8Hz,6H).
13 C NMR(100MHz,CDCI 3 ):δ(ppm)159.12,157.18,147.42,144.68,141.03,136.74,132.74,131.38,129.88,129.67,129.01,128.38,127.68,127.48,126.86,126.13,122.36,28.88,23.96,21.78.
example 15:
is synthesized by (a)
The reaction formula is:
the method comprises the following specific steps: to a 15mL pressure-resistant tube was added 0.5mmol of 2-methylquinoline, 0.75mmol of elemental iodine and 2.0mL of dimethyl sulfoxide. Sealing a pressure-resistant pipe, heating the reaction for 4-6h in an oil bath at 110 ℃, monitoring the reaction by TLC, after methylquinoline is completely converted, adding 0.5mmol of p-methylaniline, 0.5mmol of phenylpropionaldehyde and 0.25mmol of potassium carbonate into the reaction solution, continuing the reaction for 4-6h under the same conditions, cooling to room temperature after the reaction is finished, adding 50ml of water into the reaction solution, extracting the mixed solution with ethyl acetate, washing an organic layer by sodium thiosulfate and sodium hydroxide, collecting an organic phase, adding anhydrous sodium sulfate for drying, evaporating the solvent under reduced pressure to obtain a crude product, and separating and purifying the crude product by using ethyl acetate/petroleum ether=1:8 (V/V) as eluent to obtain the required product. The product is white solid, the yield is 76.8%, the melting point is 162.1-162.5 ℃, the melting range of the product is shorter, and the product is purer.
The nuclear magnetic hydrogen spectrogram result of the obtained product is as follows: 1 H NMR(400MHz,CDCI 3 ):δ(ppm)8.22(d,J＝8.6Hz,1H),8.19(dd,J＝8.5,0.6Hz,1H),8.08(d,J＝9.7Hz,1H),7.3(t,J＝8.5Hz,2H),7.86(dd,J＝8.8,1.9Hz,1H),7.77-7.73(m,1H),7.61-7.56(m,1H),7.56-7.49(m,2H),7.21-7.05(m,3H),7.03(dd,J＝8.2,2.5Hz,2H),4.61(s,2H),2.53(s,3H).
13 C NMR(100MHz,CDCI 3 ):δ(ppm)158.90,156.94,147.30,145.23,140.57,137.15,137.05,136.79,133.90,131.63,129.72,129.27,129.13,128.40,128.12,127.73,127.51,126.95,126.18,126.10,122.32,39.11,21.81.
compared with the existing method, the method has the advantages of short reaction time, mild reaction condition, good safety, convenient operation, high reaction efficiency and low catalyst cost, and is a method with potential application value.
The preferred embodiments of the present invention have been described in detail above, but the present invention is not limited to the specific details of the above embodiments, and within the scope of the technical teaching concept of the present invention, various simple modifications may be made to the technical solutions of the present invention, and the technical solutions obtained by equivalent substitution or equivalent minor transformation fall within the scope of the present invention. In addition, the specific features described in the above embodiments may be combined in any suitable manner, and in order to avoid unnecessary repetition, various possible combinations are not described further. Moreover, any combination of the various embodiments of the invention can be made without departing from the spirit of the invention, which should also be considered as disclosed herein.
Claims (6)
1. A one-pot preparation method of 2,2' -biquinoline compounds is characterized by comprising the following steps:
(1) Under the catalysis of a catalyst iodine simple substance, the compound 1 is contacted with the iodine simple substance in advance to obtain a contacted product;
；
the compound 1 is contacted with iodine simple substance in advance, and specifically comprises the following steps: adding a compound 1, an iodine simple substance and a solvent into a pressure-resistant pipe, heating in an oil bath at 60-150 ℃ for reaction for 2-8 hours, monitoring the reaction by TLC, and obtaining a product after contact after the compound 1 is completely converted;
(2) Then the product after contact is contacted with a compound 2 and a compound 3 under the catalysis of potassium carbonate; finally, extracting, washing, drying, separating and purifying to obtain the 2,2' -biquinoline compound;
；
the product after contact is contacted with a compound 2 and a compound 3 under the catalysis of potassium carbonate, and the method specifically comprises the following steps: adding a compound 2, a compound 3 and potassium carbonate into the product after contact, heating in an oil bath at 60-150 ℃ for reaction for 2-8 hours, cooling to room temperature after the reaction is finished, adding 30-50mL water into the reaction liquid, extracting the mixed liquid, washing an organic layer, collecting an organic phase, adding anhydrous sodium sulfate for drying, decompressing and evaporating a solvent to obtain a crude product, and separating and purifying the crude product to obtain the 2,2' -biquinoline compound;
the 2,2' -biquinoline compound has a structure shown in a general formula I:
；
wherein R is 1 Is hydrogen, fluorine, chlorine, bromine, phenyl, methyl, methoxy or ethoxy;
R 2 methyl, ethyl, methoxy, phenyl, chloro or bromo;
R 3 is a straight chain or branched alkane having 1 to 4 carbon atoms, benzyl or phenyl.
2. The method according to claim 1, wherein the molar ratio of the compound 1 to the compound 2 to the compound 3 is 1 (0.8-2): 0.8-2.
3. The method of claim 1, wherein the molar ratio of compound 1 to elemental iodine is 1 (1.5-3).
4. The process according to claim 1, wherein the molar ratio of compound 1 to potassium carbonate is 1 (0.1-2).
5. The method of claim 1, wherein the solvent is dimethyl sulfoxide, ethyl acetate, acetonitrile, methanol, ethanol, toluene, or chloroform.
6. The method of claim 1, wherein the extracted extractant is ethyl acetate; the washing detergent is sodium thiosulfate and sodium hydroxide; the separation and purification steps are as follows: and (3) performing column chromatography separation and purification by using a mixture of ethyl acetate and petroleum ether as leacheate, wherein the volume ratio of the ethyl acetate to the petroleum ether is 1 (1-10).
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| JPH0363261A (en) * | 1989-08-01 | 1991-03-19 | Wako Pure Chem Ind Ltd | Novel biquinoline derivative and its production |
| CN101134742A (en) * | 2007-09-30 | 2008-03-05 | 浙江工业大学 | Method for synthesizing 2,2'-biquinoline |
| CN109265473A (en) * | 2018-11-28 | 2019-01-25 | 安庆师范大学 | One kind zinc containing mixed ligand (II) metal organic complex and its preparation method and application |
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| JPH0363261A (en) * | 1989-08-01 | 1991-03-19 | Wako Pure Chem Ind Ltd | Novel biquinoline derivative and its production |
| CN101134742A (en) * | 2007-09-30 | 2008-03-05 | 浙江工业大学 | Method for synthesizing 2,2'-biquinoline |
| CN109265473A (en) * | 2018-11-28 | 2019-01-25 | 安庆师范大学 | One kind zinc containing mixed ligand (II) metal organic complex and its preparation method and application |
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